In March and April 2009, pandemic H1N1 2009 influenza A virus
(pH1N1 2009) emerged in Mexico, the United States and Canada. As of
August 6, 2010, more than 214 countries officially reported
laboratory-confirmed cases of pH1N1 2009 infection, including 18,449
deaths. (1) Of these, 8,678 laboratory-confirmed hospitalized cases of
pH1N1 2009 had been reported in all provinces and territories in Canada,
including 1,473 ICU admissions and 428 deaths. (2) Of special concern
has been the morbidity and mortality burden of this virus in First
Nation and other Aboriginal communities. While Aboriginal peoples
constitute only 3.8% of the Canadian population, from April 2009 to
April 2010, they accounted for 7.4-10% of hospitalizations due to pH1N1
2009, 7.8-10.4% of ICU admissions and 7.1-10.4% of deaths. (2) These
numbers were even higher during the first wave of the pandemic (April
12-August 29, 2009), when the rate of hospitalization of First Nations
was 72 per 100,000 population, compared to a national cumulative crude
hospitalization rate of 25.7 per 100,000 population. (2) In a study of
168 critically ill patients with pH1N1 2009 influenza in Canada during
wave 1, Aboriginal peoples accounted for 25.6% of cases. (3) As of
mid-June 2009 during the first wave of the pandemic, 24 Manitobans were
on respirators in Winnipeg intensive care units, more than two thirds of
whom were First Nations people. We herein describe what is currently
known regarding the risk of influenza among First Nations people in
Canada.

METHODS

We undertook a literature search using MEDLINE, EMBASE, PsycINFO,
CAB Abstracts, and the Arctic Health Publication Database without
language restriction from inception to December 1, 2010, with
combinations of the subject headings "First Nations",
"Canadian Aboriginals", "hospital admissions",
"pneumonia" and "influenza". Pertinent material was
also identified from bibliographic and standard reference reviews. We
included literature that referenced "Canadian Aboriginal
peoples" as a group, understanding that FN comprise the majority of
individuals in this group (FN=60%, Metis=33%, Inuit=4%, Other=3%). We
included literature reporting original epidemiologic or case series data
on hospital admissions, pneumonia and influenza in FN. In Canada,
"wave 1" of the pandemic occurred from April 12 to August 29,
2009, and "wave 2" from August 30, 2009 to April 3, 2010.

Morbidity and mortality among Canadian First Nations

It has been previously observed that Canadian First Nations (FN)
experience an excess mortality and illness burden compared to non-FN
Canadians. (4-7) FN men residing on Canadian reserves have a 65% excess
annual mortality rate compared to their non-FN counterparts, and FN
women have an excess annual mortality rate of 93%.6 In 2000, life
expectancy at birth for the Registered Indian population was estimated
at 68.9 years for males and 76.6 years for females. (8) This reflects
differences of 7.4 years and 5.2 years, respectively, from the 2001
Canadian population life expectancies. (8) Annual age-standardized
all-cause mortality rates among residents of Canadian reserves from 1979
to 1983 were 561 per 100,000 and 335 per 100,000 for FN men and women,
respectively, compared to 340 per 100,000 and 173 per 100,000 for non-FN
Canadians. (5) In comparison to non-FN Canadians, members of the FN and
other Canadian Aboriginal groups have an increased risk of death from
alcohol-related diseases, homicide, suicide and pneumonia. (5)

FN infant mortality also exceeds that in the general population.
(7) From 1986 to 1990, infant mortality rates were 13.8 per 1000 live
births among Indian infants, 16.3 per 1000 live births among Inuit
infants, and 7.3 per 1000 live births among non-Native Canadian infants.
(5) A study of FN mortality in five provinces observed a 40% excess in
neonatal mortality, and a fourfold excess of postnatal mortality. (7)

In their study of hospital admission rates among members of the
Mi'kmaq Nation in Nova Scotia, Webster et al. observed an
age-standardized admission rate of 29,347 per 100,000 Mi'kmaq
versus 20,951 per 100,000 reference Nova Scotians in the year 1999,
yielding an age-adjusted relative risk (AARR) for total hospital
admissions of 1.40. (4) Specific excess morbidity was noted among FN for
admissions related to circulatory diseases, diabetes, respiratory
diseases and pneumonia/influenza. (4)

Respiratory illness morbidity among Canadian First Nations

From the study period 1996-1999, respiratory disease was the single
leading cause of hospitalization among Mi'kmaq, with AARRs far in
excess of what was observed for non-Mi'kmaq Nova Scotians. (4)
Pneumonia and influenza accounted for more than half of respiratory
admissions versus one quarter of respiratory admissions in the reference
population. (4) In 1999, pneumonia and influenza accounted for 1,474
hospital admissions per 100,000 Mi'kmaq versus 337 hospital
admissions per 100,000 non-Mi'kmaq Nova Scotians, yielding an AARR
of 4.37.4 Stated differently, pneumonia and influenza accounted for 5.3%
of age-standardized hospital admissions among Mi'kmaq compared to
only 1.6% of admissions in the reference population. (4) FN residing in
Alberta had an age- and sex-adjusted hospitalization rate for
community-acquired pneumonia that was 5 times greater than that of
non-FN Albertans. (9) FN were also 1.4-fold more likely than non-FN
Albertans to require readmission for community-acquired pneumonia within
30 days of discharge. (9) In FN infants, the rate of hospital admission
for lower respiratory tract infection (LRTI) has been observed to be as
high as 19.8 per 100 person-years compared to 3.4 per 100 person-years
in non-FN infants, yielding a RR of 5.8. (10)

In addition to demonstrable excesses in hospital admission rates
due to influenza and pneumonia among members of FN, the overall severity
and frequency of these infections in FN children and adults also exceed
those of the general population. (7,11) In their 3-year prospective
study of pneumonia in hospitalized children, Houston et al. found that
FN children with pneumonia were more severely ill, had more prolonged
clinical symptomatology, more associated diarrhea, and longer duration
of hospitalization compared to "white" children. (11) Of 21
children <14 years of age whose chest x-rays worsened during
hospitalization for pneumonia, 20 were FN children. (11) In addition,
none of 64 "white" children died of pneumonia during their
hospitalization, compared to 4 of 102 FN children. (11) Similar findings
have been observed in studies of non-FN Aboriginal Canadians: in a
prospective study of Inuit infant hospitalizations due to lower
respiratory tract infection on Baffin Island, 12% required intubation
and mechanical ventilation, (12) which is higher than for their
non-Aboriginal counterparts. (11) For Inuit children of Baffin Island
<6 months of age, LRTIs are the primary cause for hospital admission,
medical evacuation, and overall health-related expenditures. (13,14)

In addition to more severe respiratory tract infections, FN
children have been observed to have more frequent respiratory tract
infections. Over a 1-year period, 97 FN and Inuit children studied
prospectively suffered 112 episodes of non-tuberculous pneumonia severe
enough to warrant presentation to hospital in Edmonton. (15) Of these, 2
children had a history of >6 previous episodes of pneumonia, and 34
had a history of 3-6 previous episodes, which is higher than that
observed for "white" children. (15) The age distribution
correlated well with that of all pediatric patients admitted with
pneumonia during the 12-month period studied, (15) thus, confounding by
age is an unlikely explanation for the pattern observed. In their cohort
study of 99 FN and 316 non-FN Canadian infants in southern Ontario,
Evers et al. observed that FN infants were 13 times more likely to
suffer multiple episodes of pneumonia during their first year of life.
(10) FN infants had twice as many episodes of upper respiratory tract
infections and otitis media as their non-FN counterparts. (10)

Several risk factors for increased rates of acute respiratory
infections in Canadian Aboriginal populations, including FN and Inuit,
have been postulated, including smoking, maternal smoking during
pregnancy, exposure to second-hand smoke, feeding practices, and
socio-economic factors such as low education, housing, residential
crowding, and family size. (11,13-15) In their case-control study of
risk factors for hospital admission due to viral LRTI among the Inuit
children of Baffin Island, specifically, Banerji et al. found that the
risk of admission was increased 4-fold in association with maternal
smoking during pregnancy, 3.6-fold in association with lack of
breastfeeding, and 2.5-fold in association with overcrowding at home.
(14) High rates of recurrent pneumonia in FN children were also
attributed to socio-economic and environmental factors including poor
diet, crowded living conditions, geographic isolation, and lack of
parental education, as chronic illnesses which could have accounted for
the recurrent episodes, such as asthma, cystic fibrosis,
hypogammaglobulinemia, leucopenia, or structural lung disease, were
excluded. (15)

Influenza morbidity among Canadian First Nations

New data on the burden of pH1N1 2009 influenza, specifically in the
FN and Aboriginal communities, have emerged. In their study of 168
critically ill patients with pH1N1 2009 influenza, Kumar et al. observed
that young, female, and Aboriginal patients without major comorbidities
were over-represented among the cohort. (3) When present, the most
common comorbidities were lung disease, obesity, hypertension, smoking,
and diabetes, all of which are known to be disproportionately
represented among Aboriginal peoples. (4-6) A second Manitoba study
confirmed that FN ethnicity was independently associated with an
increased risk of both mild and severe pH1N1 2009. (16) For 588
infections where ethnicity was known, FN accounted for 28% of community
cases, 54% of hospitalized cases, and 60% of those admitted to the ICU.
(16) FN were overrepresented among cases of severe pH1N1 2009 after
adjusting for age, sex, comorbidities, rural residence, income level and
treatment interval. (16) FN were 6.5 times more likely to be admitted to
an ICU. (16) Crude hospital admission and mortality rates for pH1N1 2009
in FN also exceed those of the general Canadian population. In the first
wave of the pandemic, the hospitalization rate was 72 per 100,000 for FN
compared to a national crude hospitalization rate of 25.7 per 100,000,2
and the mortality rate was 0.7 per 100,000 in FN2 compared to 0.1 per
100,000 nationally. (2) Overall, pH1N1 2009 was associated with a 3- to
8-fold elevated risk of hospitalization and death in Canadian Aboriginal
populations (including FN). Similar findings were reported for
indigenous populations of the United States, Australia, New Zealand, and
other parts of Oceania.

CONCLUSION

These data summarize the published evidence regarding risk and
proportionate morbidity attributable to respiratory illness, and in
particular, pneumonia and influenza, in Canadian FN populations. Because
testing for viral causes of respiratory infection is rarely performed,
especially in adults, it is impossible to assess the extent to which
seasonal influenza specifically contributes to the increased burden of
respiratory illness. However, the pandemic experience of excess illness,
combined with the knowledge that the burden of influenza can be
effectively mitigated with vaccination, antiviral agents, and
non-pharmaceutical interventions (e.g., hand hygiene, social
distancing), suggests that a systematic public health approach to
defining the burden of illness, and the effect of interventions to
reduce this burden, is important.

Consultation with Aboriginal peoples has identified several
challenges and solutions specific to pandemic influenza mitigation in
their communities. (17) Reported reasons for a successful pH1N1 2009
vaccination campaign in one FN community included community awareness,
support at the chief and council level, additional personnel and fiscal
resources, and teaching efforts. (18) Uptake of pH1N1 2009 vaccine in FN
communities ranged from 59-111%, (12,18) with rates above 100% accounted
for by off-reservation residents returning to their communities for
immunization. Implementing mitigation strategies, including vaccination
campaigns, in a culturally sensitive and appropriate manner with
community engagement under the direction of Aboriginal peoples and key
stakeholders should be a priority.

Although social determinants of health are strongly associated with
influenza incidence and burden, and may explain the vulnerability of FN
populations to severe disease due to pandemic influenza, the spectre of
underlying genetic susceptibilities to influenza and other respiratory
diseases in FN populations is often raised. (3) Indigenous populations
around the world have been disproportionately affected by pH1N1 2009 as
they were during the 1918 and 1957 pandemics. While immunogenetic data
exist to support genetic susceptibilities to several intracellular
pathogens, such as Mycobacterium tuberculosis, HIV, and hepatitis B and
C virus, (19) these susceptibilities are not broadly racially based, and
no data exist to provide support for the hypothesis that genetic factors
explain the over-representation of complicated influenza infection among
indigenous populations in general, or Canadian Aboriginal peoples in
particular. Adverse social determinants of health are associated with FN
ethnicity and influenza incidence and burden, and may better explain the
observed ethnic disparities.

The available literature suggests that FN persons are at least 4-5
times more likely to be hospitalized for influenza and pneumonia, and
were up to 8 times more likely to be hospitalized for pH1N1 2009, than
non-FN Canadian counterparts. This level of risk has resulted in the
Canadian National Advisory Committee on Immunization including
Aboriginal peoples in those populations considered at significantly
increased risk of influenza complications, and therefore recommended as
priority for vaccination programs. (20) While ongoing influenza
surveillance and continued investigation into biological and
socio-environmental predictors of complicated influenza infection in
Aboriginal populations are clearly needed, priority should be given to
establishing effective influenza vaccination programs in a culturally
appropriate manner with active community engagement, as was successfully
achieved in many FN communities during pH1N1 2009. (12,18) Future
pandemic planning at all levels in Canada should ensure that the
substantially elevated risk of serious illness in Aboriginal
communities, particularly those that are remote and isolated, is taken
into consideration, and that pandemic plans for Aboriginal communities
are appropriately prioritized.

(8.) Minister of Indian Affairs and Northern Development. Basic
departmental data, 2001. Ministry of Public Works and Government
Services Canada, Cat. #R12-7/2001E. Available at:
http://www.collectionscanada.gc.ca/webarchives/20071214083001/http://
www.ainc-inac.gc.ca/pr/sts/bdd01/bdd01_e.pdf (Accessed January 21,
2010).

[3.] First Nations and Inuit Health, Ontario Region, Health Canada,
Toronto, ON (at time of study; currently with Community and Health
Services Department, Regional Municipality of York, Newmarket, ON)

[4.] Dept. of Microbiology, Mount Sinai Hospital, Toronto, ON

[5.] Dept. of Laboratory Medicine and Pathobiology, University of
Toronto, Toronto, ON